The objectives of the proposed research are to determine the sensitivity and response of pre- and postnatal rat lungs to the air pollutants 03 and N02. The age span to be studied is from the 15th day of pregnancy to 35 days after birth. Recent research from this laboratory has shown that the epithelial tissue of the small airways and proximal alveoli of adult rats show significant cellular injury and destruction after short-term exposure (2-24 hrs) to low levels of 03 or N02. Between 24 and 48 hours the tissue is repaired through cell division and the new cells are resistant to the pollutants. In addition, we have also found that sustained exposure to the same levels (0.5-1.0 ppm 03 or 15-17 ppm N02) produces a sequence of events that culminates in a disease closely resembling human emphysema after 2 to 3 months. Little is known, however, about the sensitivity and response of lung tissue of the very young to these oxidizing agents. To accomplish the above goal, we will employ 4 avenues of research (structural, cell dynamics, biochemistry and cytochemistry) that are complementary to one another and together will produce a significant advance in our understanding of the fetal and post-natal lung and its ability to respond to 03 or N02. Detailed light, ultrastructural, and cell dynamic studies employing techniques developed in this laboratory which require precise selection and orientation of the tissue will provide reproducible data on various structural components of the lung. Quantitative biochemical profiles of three enzymes (glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GR), and glutathione peroxidase (GP)) and nonprotein sulfhydryl as represented by glutathione of the anerobic pathway (Fig. 1) will be analyzed at selected intervals throughout the age span to be studied. In addition, two cytochemical procedures, one for G-6-PD and the other for glutathione, will be utilized to demonstrate the specific sites in the tissue and cells where these elements are located.